We wish to define the role of certain cell surface molecules in the lytic interaction between lymphocytes and tumor cells. Two important phenomena were previously discovered under this grant: the inverse relationship between MHC antigen expression and NK sensitivity, and the ability of C3 fragments to enhance the cytotoxic effect of NK and some T-cells against certain receptor carrying targets by bridge formation. The exploration of these two phenomena constitute the main focus of the continued project. Our specific projects are as follows: I. INFLUENCE OF THE COMPLEMENT SYSTEM ON LYMPHOCYTE FUNCTIONS I.l. Contribution of NK cell adhesion molecules (leu-CAM), lymphocyte mediated cytotoxicity. I.2. Lymphocyte mediated lysis of target cells equipped with surface reactive antibodies. I.3. Activation of C3 by cells that carry surface associated virus envelope components. I.4. C3 fragment-mediated interaction between activated T-cells and B-cells. II. MHC GENE DEPENDENT CONTROL OF NATURAL TUMOR RESISTANCE II.l. Specific adaptive, natural and lymphokine activated effector mechanisms in MHC transgenic mice. II.2. MHC ligand density in antigen presentation and effector cell triggering. II.3. Natural, specific adaptive and lymphokine induced tumor immunity in the brain. II.4. The influence of host-tumor MHC-interactions on natural resistance against tumors. II.5. Novel immunotherapy strategies: expansion of the NK and LAK repertoire by manipulating of the host bone marrow genome.